Component

Human cubilin / CUBN

Human cubilin / CUBN

9 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. The 3.3-angstrom human IF-cobalamin/CUB5-8 structure showed two separated cubilin CUB domains engaging the two intrinsic factor domains.

    Human cubilin / CUBN → Human intrinsic factor-cobalamin complex source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Recombinant human proteins; X-ray crystallography, PDB 3KQ4
    exposure
    Purified IF-cobalamin plus CUB5-8 fragment
    limitations
    Partial receptor crystal structure; recognition does not by itself establish endocytosis kinetics.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Cubilin recognizes B12 carried by intrinsic factor.
    primary_references
    [andersen-2010-if-cubn] Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. (2010). https://pubmed.ncbi.nlm.nih.gov/20237569/ DOI: 10.1038/nature08874
    tissue_or_cell_type
    Extracellular ileal receptor recognition model

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 244–255

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human proteins; X-ray crystallography, PDB 3KQ4 · source_derived_draft · unverified_draft

    ### b12-abs-cubn-recognition The 3.3-angstrom human IF-cobalamin/CUB5-8 structure showed two separated cubilin CUB domains engaging the two intrinsic factor domains. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cubilin recognizes B12 carried by intrinsic factor. organism: Homo sapiens tissue_or_cell_type: Extracellular ileal receptor recognition model experimental_model: Recombinant human proteins; X-ray crystallography, PDB 3KQ4 limitations: Partial receptor crystal structure; recognition does not by itself establish endocytosis kinetics. exposure: Purified IF-cobalamin plus CUB5-8 fragment cross_nutrient: true [andersen-2010-if-cubn] Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. (2010). https://pubmed.ncbi.nlm.nih.gov/20237569/ DOI: 10.1038/nature08874
    Complete structured claim and evidence

What acts on it

  1. Human renal cubilin and AMN copurified and coeluted as a tightly associated complex that required denaturing conditions for separation.

    Human amnionless / AMN → Human cubilin / CUBN source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Affinity purification and gel filtration of human kidney membrane proteins
    exposure
    IF-cobalamin affinity chromatography; nondenaturing versus denaturing separation
    limitations
    Native renal purification establishes association; intestinal uptake rate is not measured by this experiment.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Cubilin and amnionless form a stable receptor pair.
    primary_references
    [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    tissue_or_cell_type
    Renal epithelial membranes

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 218–229

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affinity purification and gel filtration of human kidney membrane proteins · source_derived_draft · unverified_draft

    ### b12-abs-cubam-association Human renal cubilin and AMN copurified and coeluted as a tightly associated complex that required denaturing conditions for separation. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cubilin and amnionless form a stable receptor pair. organism: Homo sapiens tissue_or_cell_type: Renal epithelial membranes experimental_model: Affinity purification and gel filtration of human kidney membrane proteins limitations: Native renal purification establishes association; intestinal uptake rate is not measured by this experiment. exposure: IF-cobalamin affinity chromatography; nondenaturing versus denaturing separation cross_nutrient: false [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway.

    Human CUBN gene → Urinary loss of calcifediol source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    true
    evidence_location
    Primary abstract, cubilin sequestration and human urinary loss.
    experimental_model
    Human inherited cubilin dysfunction; supporting receptor experiments
    exposure
    Inherited CUBN dysfunction; patient details/doses not specified in retrieved abstract.
    limitations
    This shared B12/D transport machinery does not mean dietary B12 deficiency causes urinary D loss. Genotype-phenotype evidence is observational.
    nutrient
    Vitamin D2 and D3 · Vitamin D2 and D3
    nutrient_topic
    Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
    organism
    Homo sapiens
    plain_language
    Cubilin defects can cause loss of vitamin D precursor through urine.
    primary_references
    [nykjaer2001] Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). (2001). https://pubmed.ncbi.nlm.nih.gov/11717447/ DOI: 10.1073/pnas.241516998
    tissue_or_cell_type
    kidney proximal tubule and urine
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 257–270

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human inherited cubilin dysfunction; supporting receptor experiments · source_derived_draft · unverified_draft

    ### vd-act-cubilin-human-loss Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway. Condition category: machinery_impairment nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cubilin defects can cause loss of vitamin D precursor through urine. organism: Homo sapiens tissue_or_cell_type: kidney proximal tubule and urine experimental_model: Human inherited cubilin dysfunction; supporting receptor experiments limitations: This shared B12/D transport machinery does not mean dietary B12 deficiency causes urinary D loss. Genotype-phenotype evidence is observational. exposure: Inherited CUBN dysfunction; patient details/doses not specified in retrieved abstract. cross_nutrient: true evidence_location: Primary abstract, cubilin sequestration and human urinary loss. nutrient: Vitamin D2 and D3 [nykjaer2001] Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). (2001). https://pubmed.ncbi.nlm.nih.gov/11717447/ DOI: 10.1073/pnas.241516998
    Complete structured claim and evidence

  2. Two siblings with AMN p.Gln248Ter/c.208-2A>G compound heterozygosity had markedly reduced urinary cubilin receptor activity despite preserved intrinsic-factor binding affinity and no CUBN mutation.

    Human AMN p.Gln248Ter / c.208-2A>G compound genotype → Urinary cubilin intrinsic factor-binding activity source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Two affected siblings and family carriers; urinary receptor characterization
    exposure
    Inherited compound AMN nonsense/splice genotype
    limitations
    Urinary receptor activity is a localization-related readout; it is not direct intestinal flux. Heterozygous relatives were unaffected.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Faulty amnionless reduced available receptor without changing its affinity.
    primary_references
    [namour-2011-amn] Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. (2011). https://pubmed.ncbi.nlm.nih.gov/21750092/ DOI: 10.3324/haematol.2011.043984
    tissue_or_cell_type
    Renal epithelial receptor expression
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 296–307

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two affected siblings and family carriers; urinary receptor characterization · source_derived_draft · unverified_draft

    ### b12-abs-amn-human-receptor Two siblings with AMN p.Gln248Ter/c.208-2A>G compound heterozygosity had markedly reduced urinary cubilin receptor activity despite preserved intrinsic-factor binding affinity and no CUBN mutation. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Faulty amnionless reduced available receptor without changing its affinity. organism: Homo sapiens tissue_or_cell_type: Renal epithelial receptor expression experimental_model: Two affected siblings and family carriers; urinary receptor characterization limitations: Urinary receptor activity is a localization-related readout; it is not direct intestinal flux. Heterozygous relatives were unaffected. exposure: Inherited compound AMN nonsense/splice genotype cross_nutrient: false [namour-2011-amn] Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. (2011). https://pubmed.ncbi.nlm.nih.gov/21750092/ DOI: 10.3324/haematol.2011.043984
    Complete structured claim and evidence

  3. In the human IF-cobalamin/CUB5-8 structure, calcium-dependent contacts connect cubilin ligand-binding domains to intrinsic factor, providing a molecular basis for calcium-dependent recognition.

    Calcium ion → Human cubilin binding of intrinsic factor-cobalamin source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Recombinant human proteins; crystal complex at 3.3 angstrom
    exposure
    Purified complex containing calcium ions
    limitations
    Does not define a dietary calcium intake target or prove nutritional calcium deficiency causes B12 malabsorption.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Calcium helps intrinsic factor dock with the B12 receptor.
    primary_references
    [andersen-2010-if-cubn] Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. (2010). https://pubmed.ncbi.nlm.nih.gov/20237569/ DOI: 10.1038/nature08874
    tissue_or_cell_type
    Extracellular ileal receptor binding site

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 257–268

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human proteins; crystal complex at 3.3 angstrom · source_derived_draft · unverified_draft

    ### b12-abs-calcium-recognition In the human IF-cobalamin/CUB5-8 structure, calcium-dependent contacts connect cubilin ligand-binding domains to intrinsic factor, providing a molecular basis for calcium-dependent recognition. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium helps intrinsic factor dock with the B12 receptor. organism: Homo sapiens tissue_or_cell_type: Extracellular ileal receptor binding site experimental_model: Recombinant human proteins; crystal complex at 3.3 angstrom limitations: Does not define a dietary calcium intake target or prove nutritional calcium deficiency causes B12 malabsorption. exposure: Purified complex containing calcium ions cross_nutrient: true [andersen-2010-if-cubn] Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. (2010). https://pubmed.ncbi.nlm.nih.gov/20237569/ DOI: 10.1038/nature08874
    Complete structured claim and evidence

  4. Human renal cubilin and AMN remained associated during coelution in EDTA, indicating that their mutual association did not require calcium under these conditions.

    Calcium ion → Human cubilin-amnionless complex source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Human kidney cubilin-AMN purification with chelation
    exposure
    EDTA present during coelution
    limitations
    Chelation result concerns CUBN-AMN association, not IF-cobalamin docking or whole-body calcium deficiency.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Calcium dependence concerns ligand binding, not every receptor interaction.
    primary_references
    [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    tissue_or_cell_type
    Renal epithelial receptor complex

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 231–242

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human kidney cubilin-AMN purification with chelation · source_derived_draft · unverified_draft

    ### b12-abs-cubam-association-calcium Human renal cubilin and AMN remained associated during coelution in EDTA, indicating that their mutual association did not require calcium under these conditions. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium dependence concerns ligand binding, not every receptor interaction. organism: Homo sapiens tissue_or_cell_type: Renal epithelial receptor complex experimental_model: Human kidney cubilin-AMN purification with chelation limitations: Chelation result concerns CUBN-AMN association, not IF-cobalamin docking or whole-body calcium deficiency. exposure: EDTA present during coelution cross_nutrient: true [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    Complete structured claim and evidence

  5. Mapping and sequencing identified two independent disease-specific CUBN mutations across 17 Finnish families with selective intestinal cobalamin malabsorption.

    Human biallelic CUBN disease genotypes in Aminoff 1999 → Intestinal cobalamin absorption source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    17 Finnish MGA1 families; linkage and molecular analysis
    exposure
    Inherited biallelic CUBN disease genotypes
    limitations
    Family-genetic evidence; allele-specific biochemical steps require separate functional experiments.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Inherited cubilin defects can block B12 absorption.
    primary_references
    [aminoff-1999-cubn] Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. (1999). https://pubmed.ncbi.nlm.nih.gov/10080186/ DOI: 10.1038/6831
    tissue_or_cell_type
    Small-intestinal absorption
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 283–294

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 17 Finnish MGA1 families; linkage and molecular analysis · source_derived_draft · unverified_draft

    ### b12-abs-cubn-genetic-malabsorption Mapping and sequencing identified two independent disease-specific CUBN mutations across 17 Finnish families with selective intestinal cobalamin malabsorption. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited cubilin defects can block B12 absorption. organism: Homo sapiens tissue_or_cell_type: Small-intestinal absorption experimental_model: 17 Finnish MGA1 families; linkage and molecular analysis limitations: Family-genetic evidence; allele-specific biochemical steps require separate functional experiments. exposure: Inherited biallelic CUBN disease genotypes cross_nutrient: false [aminoff-1999-cubn] Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. (1999). https://pubmed.ncbi.nlm.nih.gov/10080186/ DOI: 10.1038/6831
    Complete structured claim and evidence

  6. The human cubilin P1297L CUB5-8 fragment showed severalfold higher dissociation constant for IF-cobalamin than wild type, mainly from a lower association rate.

    Human cubilin P1297L variant → Human intrinsic factor-cobalamin complex source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Human wild-type/P1297L fragments expressed in CHO cells; SPR
    exposure
    Site-directed P1297L substitution
    limitations
    Fragment binding assay; not every CUBN variant shares this mechanism.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    This cubilin variant binds its B12 carrier less efficiently.
    primary_references
    [kristiansen-2000-p1297l] Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. (2000). https://pubmed.ncbi.nlm.nih.gov/10887099/ DOI: 10.1182/blood.v96.2.405
    tissue_or_cell_type
    Ileal receptor ligand-binding model
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 270–281

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human wild-type/P1297L fragments expressed in CHO cells; SPR · source_derived_draft · unverified_draft

    ### b12-abs-cubn-p1297l-affinity The human cubilin P1297L CUB5-8 fragment showed severalfold higher dissociation constant for IF-cobalamin than wild type, mainly from a lower association rate. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This cubilin variant binds its B12 carrier less efficiently. organism: Homo sapiens tissue_or_cell_type: Ileal receptor ligand-binding model experimental_model: Human wild-type/P1297L fragments expressed in CHO cells; SPR limitations: Fragment binding assay; not every CUBN variant shares this mechanism. exposure: Site-directed P1297L substitution cross_nutrient: false [kristiansen-2000-p1297l] Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. (2000). https://pubmed.ncbi.nlm.nih.gov/10887099/ DOI: 10.1182/blood.v96.2.405
    Complete structured claim and evidence

  7. In the renal biopsy of the studied patient carrying CUBN G653R, cubilin and AMN localized with the ER marker instead of normal brush-border localization.

    Human cubilin G653R variant → Human cubilin-amnionless retention in endoplasmic reticulum source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    One IGS patient renal biopsy compared with a control biopsy
    exposure
    Patient CUBN G653R; co-occurring AMN P295S also reported
    limitations
    One patient; AMN P295S contribution was inconclusive. This tissue observation alone cannot assign all disease causality to G653R.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    The patient receptor proteins accumulated inside kidney cells.
    primary_references
    [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    tissue_or_cell_type
    Human renal proximal tubular epithelium
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 348–359

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · One IGS patient renal biopsy compared with a control biopsy · source_derived_draft · unverified_draft

    ### b12-abs-human-g653r-er In the renal biopsy of the studied patient carrying CUBN G653R, cubilin and AMN localized with the ER marker instead of normal brush-border localization. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The patient receptor proteins accumulated inside kidney cells. organism: Homo sapiens tissue_or_cell_type: Human renal proximal tubular epithelium experimental_model: One IGS patient renal biopsy compared with a control biopsy limitations: One patient; AMN P295S contribution was inconclusive. This tissue observation alone cannot assign all disease causality to G653R. exposure: Patient CUBN G653R; co-occurring AMN P295S also reported cross_nutrient: false [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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